Polycystic ovary syndrome (PCOS) is associated with obesity and low grade inflammation and the risk for cardiovascular disease (CVD) could be increased in PCOS.
National register-based study ...including women with PCOS and no previous diagnosis of CVD, hypertension, or dyslipidemia. PCOS Denmark (N = 18,112) included women with PCOS in the Danish National Patient Register. PCOS Odense University Hospital (OUH, N = 1165) was an embedded cohort including premenopausal women with PCOS and clinical and biochemical examination. Three age-matched controls were included per patient in PCOS Denmark (N = 52,769). The main study outcome was CVD events including hypertension and dyslipidemia defined according to nationwide in- and outpatient hospital contact diagnosis codes and/or inferred from filled medicine prescriptions.
The age at inclusion was median (quartiles) 29 (23-35) years and follow up was 11.1 (6.9-16.0) years. The Hazard ratio (95% CI) for development of CVD in PCOS Denmark was 1.7 (1.7; 1.8) (P < 0.001) and the total event rate of CVD was 22.6 per 1000 patient years in PCOS Denmark vs. 13.2 per 1000 patient years in controls (P < 0.001). The median age at diagnosis of CVD was 35 (28-42) years in PCOS Denmark vs. 36 (30-43) years in controls (P < 0.001). Obesity, diabetes, and infertility, and previous use of oral contraceptives were associated with increased risk of development of CVD in PCOS Denmark (P < 0.001). Women in PCOS OUH resembled women in PCOS Denmark regarding risk of CVD. Age, BMI, blood pressure, lipid status, and glycemic status predicted development of CVD in PCOS OUH.
The event rate of CVD including hypertension and dyslipidemia was higher in PCOS compared to controls. The risk of developing CVD must be considered even in young women with PCOS.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Endoscopic pituitary surgery has shown promising results. This study reports the experiences of experienced microscopic pituitary surgeons changing to the endoscopic technique, and the beneficial ...effects on the postoperative outcomes. 45 transsphenoidal endoscopic-assisted surgeries performed in 2016-2017 were compared with 195 microscope-assisted surgeries performed in 2007-2017 for pituitary adenoma. Tumour size, hormonal status and vision were assessed preoperatively and 3-5 months postoperatively. Cases were identified through electronic patient records. GTR was achieved in 39% of the endoscopic operations vs. 22% of microscopic operations, p = 0.018. Mean duration of surgery was 86 min (77-95) with the endoscopic technique vs. 106 min (101-111) with the microscopic technique, p < 0.001. New hypothalamus-pituitary-adrenal axis deficiencies were observed after 3% of endoscopic vs. 34% microscopic operations, p = 0.001, and overall fewer postoperative pituitary deficiencies were observed in the endoscope-assisted group. Complications within 30 days of surgery occurred in 17% of endoscopic operations vs. 27% of microscopic operations (p > 0.05). Normalization of visual impairment occurred in 37% of the cases with preoperative visual impairment in the endoscopic group vs. 35% of those in the microscopic group (p > 0.05). The endoscopic technique performed better as a surgical procedure for pituitary adenomas. We found no statistically significant differences in complication rate or visual improvement between the two techniques.
Mitochondrial Respiration Is Decreased in Skeletal Muscle of Patients With Type 2 Diabetes
Martin Mogensen 1 ,
Kent Sahlin 1 2 3 ,
Maria Fernström 2 3 ,
Dorte Glintborg 4 ,
Birgitte F. Vind 4 ,
...Henning Beck-Nielsen 4 and
Kurt Højlund 4
1 Institute of Sports Science and Clinical Biomechanics, University of Southern Denmark, Odense, Denmark
2 Stockholm University College of Physical Education and Sports, GIH, Stockholm, Sweden
3 Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
4 Department of Endocrinology, Diabetes Research Centre, Odense University Hospital, Odense, Denmark
Address correspondence and reprint requests to Kurt Højlund, MD, PhD, Diabetes Research Centre, Department of Endocrinology,
Odense University Hospital, Kloevervaenget 6, 3, DK-5000 Odense C, Denmark. E-mail: k.hojlund{at}dadlnet.dk
Abstract
We tested the hypothesis of a lower respiratory capacity per mitochondrion in skeletal muscle of type 2 diabetic patients
compared with obese subjects. Muscle biopsies obtained from 10 obese type 2 diabetic and 8 obese nondiabetic male subjects
were used for assessment of 3-hydroxy-Acyl-CoA-dehydrogenase (HAD) and citrate synthase activity, uncoupling protein (UCP)3
content, oxidative stress measured as 4-hydroxy-2-nonenal (HNE), fiber type distribution, and respiration in isolated mitochondria.
Respiration was normalized to citrate synthase activity (mitochondrial content) in isolated mitochondria. Maximal ADP-stimulated
respiration (state 3) with pyruvate plus malate and respiration through the electron transport chain (ETC) were reduced in
type 2 diabetic patients, and the proportion of type 2X fibers were higher in type 2 diabetic patients compared with obese
subjects (all P < 0.05). There were no differences in respiration with palmitoyl- l -carnitine plus malate, citrate synthase activity, HAD activity, UCP3 content, or oxidative stress measured as HNE between
the groups. In the whole group, state 3 respiration with pyruvate plus malate and respiration through ETC were negatively
associated with A1C, and the proportion of type 2X fibers correlated with markers of insulin resistance ( P < 0.05). In conclusion, we provide evidence for a functional impairment in mitochondrial respiration and increased amount
of type 2X fibers in muscle of type 2 diabetic patients. These alterations may contribute to the development of type 2 diabetes
in humans with obesity.
ETC, electron transport chain
FFA, free fatty acid
HAD, 3-hydroxy-Acyl-CoA-dehydrogenase
HNE, 4-hydroxy-2-nonenal
HOMA-IR, homeostasis model assessment of insulin resistance
RCI, respiratory control index
ROS, reactive oxygen species
UCP, uncoupling protein
Footnotes
Published ahead of print at http://diabetes.diabetesjournals.org on 9 March 2007. DOI: 10.2337/db06-0981.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore
be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Accepted February 26, 2007.
Received July 17, 2006.
DIABETES
Objective To compare the metabolic profiles of normo- and hyperandrogenic women with polycystic ovary syndrome (PCOS) with those of control women at different ages during reproductive life. Design ...Case-control study. Setting Not applicable. Patient(s) In all, 1,550 women with normoandrogenic (n = 686) or hyperandrogenic (n = 842) PCOS and 447 control women were divided into three age groups: <30, 30–39, and >39 years). Interventions(s) None. Main Outcome Measure(s) Body mass index (BMI), waist circumference, blood pressure, glucose, insulin, cholesterol, lipoproteins, triglycerides and high-sensitivity C-reactive protein. Result(s) Both normo- and hyperandrogenic women with PCOS were more obese, especially abdominally. They had increased serum levels of insulin (fasting and in oral glucose tolerance tests), triglycerides, low-density lipoprotein, and total cholesterol, higher blood pressure, and lower high-density lipoprotein levels independently from BMI compared with the control population as early as from young adulthood until menopause. The prevalence of metabolic syndrome was two- to fivefold higher in women with PCOS compared with control women, depending on age and phenotype, and the highest prevalence was observed in hyperandrogenic women with PCOS at late reproductive age. Conclusion(s) When evaluating metabolic risks in women with PCOS, androgenic status, especially abdominal obesity and age, should be taken into account, which would allow tailored management of the syndrome from early adulthood on.
•Prenatal exposure to MnBP was related to lower testosterone in 3–4 months old boys.•Maternal phthalate exposure was related to lower T/LH ratio in 3–4 months old boys.•Anti-androgenic phthalates may ...affect mini-puberty occurring at 3–4 months of age.
Phthalates are plastic softeners with anti-androgenic properties. Prenatal exposure has led to lower testosterone (T) levels and smaller testicles in adult rats. To our knowledge, no studies have examined associations between prenatal phthalate exposure and sex hormone concentrations in infants.
To study associations between phthalate exposure in Danish pregnant women and T, luteinizing hormone (LH), follicle stimulating hormone (FSH), Δ4-androstenedione (adion), 17α-hydroxyprogesterone (17-OHP) dehydroepiandrosterone sulfate (DHEAS) concentrations in their infants (N = 479) during mini-puberty.
Concentrations of 12 phthalate metabolites from six phthalate diesters were measured in urine samples collected from 2010 to 2012 from 479 pregnant women participating in the Odense Child Cohort at gestational week 28 (range 20.4–30.4). Serum T, LH, FSH, adion, 17-OHP, DHEAS, weight and height were measured approximately three months after expected date of birth. Associations between prenatal phthalate exposure and gonadotropin and androgen metabolite concentrations were estimated in boys and girls separately in adjusted linear regression models.
T concentration was lower in boys prenatally exposed to phthalates. Maternal urinary concentrations of summed mono-iso-butyl and mono-n-butyl phthalate (∑MBPi+n) and summed metabolites of di-iso-nonyl phthalate (∑DiNPm) were associated with lower T/LH ratio in male offspring and a dose-response association was found. FSH was 14% (95% CI: 1; 25) lower among male offspring from mothers exposed to ∑DiNPm in the highest compared to the lowest tertile. No association was found for girls.
Even in these low exposed children, we found a significant decrease in T/LH ratio during mini-puberty in boys prenatally exposed to phthalates, which may suggest impairment of Leydig cells. The children will be followed as they approach adrenarche and pubarche in order to assess if long-term adverse effects persist.
Abstract
Background
Osteoarthritis (OA) is the most common form of arthritis with multiple risk factors implicated including female sex and obesity. Metabolic dysregulation associated with obesity ...leading to metabolic syndrome is a proposed component of that association. Polycystic ovary syndrome (PCOS) commonly affects women of reproductive age and these women are at higher risk of developing metabolic syndrome and thus likely to represent a high-risk group for early OA development. There are no published studies exploring the epidemiology of knee, hip and hand OA in women diagnosed with PCOS.
Study aim
To assess the prevalence and incidence of knee, hip and hand osteoarthritis (OA) in women with polycystic ovary syndrome (PCOS) when compared with age-matched controls.
Methods
Prospective Danish national registry-based cohort study. The prevalence of OA in 2015 and incidence rates of OA over 11.1 years were calculated and compared in more than 75,000 Danish women with either a documented diagnosis of PCOS ± hirsutism (during the period of 1995 to 2012) or age-matched females without those diagnoses randomly drawn from the same population register.
Results
In 2015, the prevalence of hospital treated knee, hip and hand OA was 5.2% in women with PCOS diagnosis. It was 73% higher than that seen in age-matched controls. Significantly higher incidence rates were observed in the PCOS cohort compared with the age-matched controls during the follow-up period (up to 20 years), with the following hazard ratios (HR): 1.9 (95% CI 1.7 to 2.1) for knee, 1.8 (95% CI 1.3–2.4) for hand and 1.3 (95% CI 1.1 to 1.6) for hip OA. After excluding women with obesity, similar associations were observed for knee and hand OA. However, risk of developing hip OA was no longer significant.
Conclusions
In this large prospective study, women with PCOS diagnosis had higher prevalence and accelerated onset of OA of both weight and non-weight bearing joints, when compared with age-matched controls. Further studies are needed to understand the relative effect of metabolic and hormonal changes linked with PCOS and their role in promoting development of OA.
To date, little is known about differences in the knowledge, diagnosis making and treatment strategies of health care providers regarding polycystic ovary syndrome (PCOS) across different disciplines ...in countries with similar health care systems. To inform guideline translation, we aimed to study physician reported awareness, diagnosis and management of PCOS and to explore differences between medical disciplines in the Nordic countries and Estonia.
This cross-sectional survey was conducted among 382 endocrinologists and obstetrician-gynaecologists in the Nordic countries and Estonia in 2015-2016. Of the participating physicians, 43% resided in Finland, 18% in Denmark, 16% in Norway, 13% in Estonia, and 10% in Sweden or Iceland, and 75% were obstetrician-gynaecologists. Multivariable logistic regression models were run to identify health care provider characteristics for awareness, diagnosis and treatment of PCOS.
Clinical features, lifestyle management and comorbidity were commonly recognized in women with PCOS, while impairment in psychosocial wellbeing was not well acknowledged. Over two-thirds of the physicians used the Rotterdam diagnostic criteria for PCOS. Medical endocrinologists more often recommended lifestyle management (OR = 3.6, CI 1.6-8.1) or metformin (OR = 5.0, CI 2.5-10.2), but less frequently OCP (OR = 0.5, CI 0.2-0.9) for non-fertility concerns than general obstetrician-gynaecologists. The physicians aged <35 years were 2.2 times (95% CI 1.1-4.3) more likely than older physicians to recommend lifestyle management for patients with PCOS for fertility concerns. Physicians aged 46-55 years were less likely to recommend oral contraceptive pills (OCP) for patients with PCOS than physicians aged >56 (adjusted odds ratio (OR) = 0.4, 95% CI 0.2-0.8).
Despite well-organized healthcare, awareness, diagnosis and management of PCOS is suboptimal, especially in relation to psychosocial comorbidities, among physicians in the Nordic countries and Estonia. Physicians need more education on PCOS and evidence-based information on Rotterdam diagnostic criteria, psychosocial features and treatment of PCOS, with the recently published international PCOS guideline well needed and welcomed.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
As a universally common endocrinopathy in women of reproductive age, the polycystic ovarian syndrome is characterized by composite clinical phenotypes reflecting the contributions of reproductive ...impact of ovarian dysfunction and metabolic abnormalities with widely varying symptoms resulting from interference of the genome with the environment through integrative biological mechanisms including epigenetics. We have performed a genome-wide DNA methylation analysis on polycystic ovarian syndrome and identified a substantial number of genomic sites differentially methylated in the whole blood of PCOS patients and healthy controls (52 sites, false discovery rate < 0.05 and corresponding p value < 5.68e-06), highly consistently replicating biological pathways extensively implicated in immunity and immunity-related inflammatory disorders (false discovery rate < 0.05) that were reportedly regulated in the DNA methylome from ovarian tissue under PCOS condition. Most importantly, our genome-wide profiling focusing on PCOS patients revealed a large number of DNA methylation sites and their enriched functional pathways significantly associated with diverse clinical features (levels of prolactin, estradiol, progesterone and menstrual cycle) that could serve as novel molecular basis of the clinical heterogeneity observed in PCOS women.
Background: Polycystic ovary syndrome (PCOS) is associated with obesity and increased risk for type 2 diabetes (T2D). However, the prospective risk of T2D in normal weight women with PCOS is debated, ...together with the relevant prospective screening programs for T2D in normal weight women with PCOS. Aim: To review and discuss prospective risk of T2D in normal weight women with PCOS, and to give recommendations regarding prospective screening for T2D in normal weight women with PCOS. Methods: Systematic review. Results: A systematic literature search resulted in 15 published prospective studies (10 controlled studies and 5 uncontrolled studies) regarding risk of T2D in study cohorts of PCOS, where data from normal weight women with PCOS were presented separately. In controlled studies, higher risk of T2D in normal weight women with PCOS compared to controls was reported in 4/10 studies, which included one study where T2D diagnosis was based on glucose measurement, two register-based studies, and one study where diagnosis of T2D was self-reported. Six of the 10 controlled studies reported no increased risk of T2D in normal weight women with PCOS. Four of these studies based the diagnosis of T2D on biochemical measurements, which supported the risk of surveillance bias in PCOS. In uncontrolled studies, 2/5 reported a higher risk of T2D in lean women with PCOS compared to the general population. We discuss the evidence for insulin resistance and β-cell dysfunction in normal weight women with PCOS, and aggravation in the hyperandrogenic phenotype, ageing women, and women with Asian ethnicity. Impaired glucose tolerance could be an important metabolic and vascular risk marker in PCOS. Conclusions: The risk of T2D may be increased in some normal weight women with PCOS. Individual risk markers such as hyperandrogenism, age >40 years, Asian ethnicity, and weight gain should determine prospective screening programs in normal weight women with PCOS.
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